Gastric cancer, or stomach cancer, originates in any part of the stomach, but can spread to other organs such as the esophagus, liver, lungs, and lymph nodes. Most gastric cancers (90%) are intestinal-type or diffuse-type adenocarcinomas, but carcinoid and stromal tumors also occur, while lymphomas (MALTomas or MALT lymphoma) represent of about 5% of gastric malignancies. The main risk factor for most gastric cancer cases (65–80%) is Helicobacter pylori infection, while about 10 percent of cases have a genetic component, such as the newly discovered Hereditary Diffuse Gastric Cancer (HDGC). Diet seems to play a role as it relates to H. pylori infection and general cancer prevention, and smoking doubles the risk of developing gastric cancer, especially in the upper part of the stomach near the esophagus. The prognosis of the disease is very poor because gastric cancer fails to display specific stages until it becomes advanced. Treatment options are therefore limited to those also typical of other late-stage cancers, such as surgery, chemotherapy, and radiation. Improving prognosis requires identifying early molecular markers of the disease, and progress has at least been made in identifying pathways key to the cancer’s progression. Pathways affected by gastric cancer normally regulate cell growth and differentiation including cell cycle, hedgehog, PI3K/AKT, Notch, TGFβ/BMP, and WNT. The fact that gastric cancer affects 3 times as many men than women suggests a protective effect by estrogen and its signaling pathways. A synergistic effect between gastrin signaling and inflammation as well as the COX2 pathway has also been suggested to contribute to gastric cancer progression. Deregulated genes and differentially methylated promoters are routinely detected in molecular analysis of gastric cancer samples and in high-throughput microarray profiling studies that can be followed up using other molecular analyses.